A comparison of intraperitoneal and oral gavage administration in comet assay in mouse eight organs

Citation
K. Sekihashi et al., A comparison of intraperitoneal and oral gavage administration in comet assay in mouse eight organs, MUT RES-GTE, 493(1-2), 2001, pp. 39-54
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
ISSN journal
1383-5718 → ACNP
Volume
493
Issue
1-2
Year of publication
2001
Pages
39 - 54
Database
ISI
SICI code
1383-5718(20010627)493:1-2<39:ACOIAO>2.0.ZU;2-Q
Abstract
One of the important advantages of the comet assay is its ability to detect genotoxicity in many different organs. Since the exposure route of the tes t compounds is likely to influence the genotoxicity detected in a given org an, it is an important factor to consider when conducting the assay. In thi s study, we compared the effects of numerous model compounds on eight organ s when administered to mice by intraperitoneal (i.p.) injection and oral (p .o.) gavage. Groups of four mice were treated once i.p. or p.o. at the identical proport ion of LD50 for each route, and the stomach, colon, liver, kidney, bladder, lung, brain, and bone marrow were sampled 3, 8, and 24h after treatment. F or 19 of the 20 tested mutagens with various modes of action, genotoxicity in some organs varied with treatment route; only the genotoxicity of methyl methane sulfonate was not affected. Treatment route, however, did not prod uce a qualitative difference in the genotoxicity of promutagens at the site s of conversion to ultimate mutagens, with aromatic hydrocarbons as the exc eption. When chemicals with positive responses in at least one organ were c onsidered to be comet assay-positive, the administration route made no diff erence. Since azo reduction is mediated by azo reductase synthesized in the gastrointestinal wall and by gut microflora and i,p.-administered azo dyes bypass their activation site (colon), the administration route is expected to make a difference in their in vivo genotoxicity. Direct-acting mutagens are expected to affect the mucosa of the gastrointestinal tract when given p.o. For those mutagens, however, the administration route did not make a qualitative difference in gastrointestinal tract genotoxicity. Moreover, al though the gastrointestinal mucosa is the first site to be exposed to p.o. administered agents, the peak times in the stomach tended to be the same as in most other organs. Based on those results, we concluded that the genoto xicity at high exposures was due to a systemic effect, and that both routes are acceptable for the comet assay when the liver and gastrointestinal org ans are sampled, so long as appropriate dose levels for systemic exposure a re selected for each route. (C) 2001 Elsevier Science B.V. All rights reser ved.